title: MyD88 signaling is not essential for induction of antigen-specific B cell responses but is indispensable for protection against Streptococcus pneumoniae infection following oral vaccination with attenuated Salmonella expressing PspA antigen.
abstract: TLRs directly induce innate host defense responses, but the mechanisms of TLR-mediated adaptive immunity remain subject to debate. In this study, we clarified a role of TLR-mediated innate immunity for induction of adaptive immunity by oral vaccination with a live recombinant attenuated Salmonella enteric serovar Typhimurium vaccine (RASV) strain expressing Streptococcus pneumoniae surface protein A (PspA) Ag. Of note, oral or intranasal vaccination with RASV expressing PspA resulted in identical or even significantly higher levels of PspA-specific IgG and IgA responses in the systemic and mucosal compartments of MyD88(-/-) mice of either BALB/c or C57BL/6 background when compared with those of wild-type mice. Although PspA-specific CD4(+) T cell proliferation in the MyD88(-/-) mice was minimal, depletion of CD4(+) T cells abolished PspA-specific IgG and IgA responses in the MyD88(-/-) mice of BALB/c background. Of the greatest interest, MyD88(-/-) mice that possessed high levels of PspA-specific IgG and IgA responses but minimal levels of CD4(+) T cell responses died earlier than nonvaccinated and vaccinated wild-type mice following i.v. or intranasal challenge with virulent S. pneumoniae. Taken together, these results suggest that innate immunity activated by MyD88 signals might not be necessary for Ag-specific Ab induction in both systemic and mucosal sites but is critical for protection following oral vaccination with attenuated Salmonella expressing PspA.
authors.affiliation: Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Park
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Doo-Hee
authors.initials: DH
authors.lastname: Shim
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022562:Salmonella Vaccines; D051193:Toll-Like Receptors; D014613:Vaccines, Attenuated; C051592:pneumococcal surface protein A